Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight  

作　　者：J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason 

机构地区：[1]Department of Physiology and Biophysics,Weill Cornell Medicine,Cornell University,New York,NY 10021,USA [2]The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine,Weill Cornell Medicine,New York,NY 10021,USA [3]Department of Immunology,Weill Cornell Medicine,Cornell University,New York,NY 10021,USA [4]Department of Stem Cell Biology and Regenerative Medicine,Keck School of Medicine,University of Southern California,Los Angeles,CA 90033,USA [5]Space Exploration Technologies Corporation,Hawthome,CA 90250,USA [6]Sovaris Aerospace,Boulder,CO 80302,USA [7]Advanced Pattern Analysis&Human Performance Group,Boulder,CO 80302,USA [8]Children's Cancer and Blood Foundation Laboratories,Departments of Pediatrics and Cell and Developmental Biology,Drukier Institute for Children's Health,Meyer Cancer Center,Weill Cornell Medicine,New York,NY 10021,USA [9]Meyer Cancer Center,Weill Cornell Medicine,New York,NY 10065,USA [10]Department of Nutrition and Integrative Physiology,Florida State University,Tallahassee,FL 32306,USA [11]Department of Systems Engineering,Colorado State University,Fort Collins,CO 80523,USA [12]Element Biosciences,San Diego,CA 10055,USA [13]Department of Environmental and Radiological Health Sciences,Colorado State University,Fort Collins,CO 80523,USA [14]Cell and Molecular Biology Program,Colorado State University,Fort Collins,CO 80523,USA [15]BioAstra Inc,New York,NY,USA [16]Washington University St Louis Oncology Division,St.Louis,MO 63100,USA [17]Meinig School of Biomedical Engineering,Cornell University,Ithaca,NY 14853,USA [18]The Feil Family Brain and Mind Research Institute,Weill Cornell Medicine,NY 10021,USA [19]WorldQuant Initiative for Quantitative Prediction,Weill Cornell Medicine,New York,NY 10021,USA

出　　处：《Precision Clinical Medicine》2024年第1期1-13,共13页精准临床医学（英文）

基　　金：supported by the Leukemia and Lymphoma Society (Grants No.LLS 9238-16 and MCL7001-18);the National Institutes of Health (Grants No.P01CA214274,R01CA249054 and R01MH117406);the WorldQuant Foundation,NASA (Grants No.80NSSC19K0432,80NSSC22K0254,NNH18ZTT001N-FG2,NNX13AE45G,NNX14AH50G,NNX17AB26G).

摘　　要：Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关 键 词：genomes CLONAL HEMATOPOIESIS STABILITY IMMUNE mitochondria RIBOSOMES SPACEFLIGHT 

分 类 号：R749.7[医药卫生—神经病学与精神病学]